Cellular Haemostaseology – Diagnosis and Therapeutic Monitoring of Inherited and Acquired Functional Platelet Disorders

Abstract

Platelets execute a key function in the regulation of haemostasis, clot stability and retraction, vascular tone and repair as well as in host defence. In exerting their function, platelets, as the central elements of cellular haemostasis, show a finetuned, intricate, activation state-dependent interaction with mediators of the plasmatic coagulation system and platelet activators, with circulating and resident cells such as leucocytes, platelets themselves, endothelial and vascular smooth muscle cells as well as with the subcellular matrix. Platelet activation is a tightly regulated process, allowing the immediate recognition of vascular damage leading to platelet activation and ultimately to formation of the primary haemostatic plug, a process which normally is self-limited and under straight control. Consequently, minor disturbances of this balanced homeostasis may result in pronounced platelet dysfunction, which has a major impact on many pathophysiological processes such as thrombosis, haemorrhage, inflammation, atherogenesis and cardiovascular disease but also on tumour growth and metastasis as well as on the anti-microbial host defence. Alterations of the functional capacity of platelets have been associated with the prognosis and severity of distinct clinical diseases, including cardiovascular diseases, diabetes, tumour metastasis and sepsis. Even though primary (hereditary) platelet functional abnormalities are very rare disorders, acquired platelet function abnormalities are relatively frequent and occur in the context of many diseases and may be mediated iatrogenically by therapeutic administration of drugs. The clinical presentation of primary or secondary platelet function disorders is very variable. Given the importance of platelets for cellular haemostasis, the recognition of platelet function disturbances, the impact of therapeutic suppression during treatment with anti-platelet medications as well as the proper selection of diagnostic tests for diagnosis and for their application as preventive risk markers is of utmost relevance for rational clinical use.